Safety and effectiveness of daptomycin across a hospitalized obese population: results of a multicenter investigation in the southeastern United States

Pharmacotherapy. 2013 Dec;33(12):1322-30. doi: 10.1002/phar.1298. Epub 2013 May 26.

Abstract

Study objective: Data are limited for antimicrobial outcomes in obese patients. This study investigated the safety and clinical outcomes of daptomycin therapy in a hospitalized obese population in the southeastern United States.

Design: Multicenter retrospective cohort study.

Setting: Thirteen hospitals in the southeastern United States.

Patients: A total of 126 hospitalized adult obese patients (body mass index [BMI] more than 30 kg/m(2) ) admitted from January 2005 through May 2010 who received daptomycin dosed on actual body weight for any indication for a minimum of 7 days.

Measurements and main results: Primary safety outcomes included incidence of creatine phosphokinase (CPK) elevations more than 1000 units/L, more than 500 units/L, myalgias, and discontinuation of therapy due to adverse drug events (ADEs). Patients were stratified by BMI class (I, II, or III) for analyses. The average weight was 121 kg, and 39% of patients were considered morbidly obese. Factors associated with an increased risk of primary safety outcomes were assessed through regression analysis. Clinical effectiveness was evaluated as a secondary outcome. CPK elevations more than 1000 units/L occurred in 8.4% of evaluable patients and specifically in 1 (3.6%), 3 (10.3%), and 4 (10.5%) patients in BMI class I, II, and III, respectively (p=0.554). CPK elevations more than 500 units/L occurred in 13.7% of patients with no statistically significant difference noted across BMI classes. Discontinuation due to ADEs occurred in 8 patients (6.3%). One patient developed rhabdomyolysis on day 9 of therapy. Clinical effectiveness was documented in 71% of patients and was consistent across BMI classes.

Conclusion: Although elevations in CPK increased in high-risk obese patients on daptomycin, discontinuation rates due to ADEs remained low. Further evaluation in a prospective trial is warranted.

Keywords: HMG Co-A reductase; Staphylococcus aureus; creatine phosphokinase; daptomycin; morbid obesity; obesity.

Publication types

  • Multicenter Study

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Infections / drug therapy*
  • Body Weight
  • Cohort Studies
  • Creatine Kinase / metabolism
  • Daptomycin / administration & dosage
  • Daptomycin / adverse effects
  • Daptomycin / therapeutic use*
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Obesity / complications*
  • Obesity, Morbid / complications
  • Regression Analysis
  • Retrospective Studies
  • Southeastern United States
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Creatine Kinase
  • Daptomycin